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relates to hypoxia and immunosuppressive pathways","volume":"259","author":"Giatromanolaki","year":"2020","journal-title":"Life Sci"},{"key":"ref89","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1007\/s10565-024-09951-9","article-title":"The roles of lactate and the interplay with m6A modification in diseases","volume":"2","author":"Tang","year":"2024","journal-title":"Cell Biol Toxicol"},{"key":"ref90","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/s41419-024-07128-0","article-title":"YTHDF1 boosts the lactate accumulation to potentiate cervical cancer cells immune escape","volume":"15","author":"Xiong","year":"2024","journal-title":"Cell Death Dis"},{"key":"ref91","doi-asserted-by":"crossref","first-page":"1381061","DOI":"10.3389\/fimmu.2024.1381061","article-title":"Clinical biomarkers for thyroid immune-related adverse events in patients with stage III and IV gastrointestinal tumors","volume":"15","author":"Xing","year":"2024","journal-title":"Front Immunol"},{"key":"ref92","doi-asserted-by":"crossref","first-page":"E486","DOI":"10.1186\/s12890-024-03055-0","article-title":"Clinical significance of pleural fluid lactate dehydrogenase\/adenosine deaminase ratio in the diagnosis of tuberculous pleural effusion","volume":"24","author":"Zhao","year":"2024","journal-title":"BMC Pulm Med"},{"key":"ref93","doi-asserted-by":"crossref","first-page":"e18043","DOI":"10.7717\/peerj.18043","article-title":"Diagnostic performance of serum metabolites biomarker associated with colorectal adenoma: a systematic review","volume":"12","author":"Abu Bakar","year":"2024","journal-title":"PeerJ"},{"key":"ref94","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.jconrel.2023.03.026","article-title":"HIF-1 inhibitor-based one-stone-two-birds strategy for enhanced cancer chemodynamic-immunotherapy","volume":"356","author":"Zhang","year":"2023","journal-title":"J Control Release Off J Control Release Soc"},{"key":"ref95","doi-asserted-by":"crossref","first-page":"100227","DOI":"10.1016\/j.xcrm.2021.100227","article-title":"Hypoxia-sensing CAR T cells provide safety and efficacy in treating solid tumors","volume":"2","author":"Kosti","year":"2021","journal-title":"Cell Rep Med"},{"key":"ref96","doi-asserted-by":"crossref","first-page":"239","DOI":"10.31635\/ccschem.019.20190010","article-title":"Oxygen nanoshuttles for tumor oxygenation and enhanced cancer treatment","volume":"1","author":"Feng","year":"2019","journal-title":"CCS Chem"},{"key":"ref97","doi-asserted-by":"crossref","first-page":"252","DOI":"10.3389\/fphys.2020.00097","article-title":"Hyperoxia during exercise: impact on adenosine plasma levels and hemodynamic data","volume":"11","author":"Boussuges","year":"2020","journal-title":"Front Physiol"},{"key":"ref98","doi-asserted-by":"crossref","first-page":"e0187314","DOI":"10.1371\/journal.pone.0187314","article-title":"Hypoxia and hypoxia-inducible factor (HIF) downregulate antigen-presenting MHC class I molecules limiting tumor cell recognition by T cells. Simos G, editor","volume":"12","author":"Sethumadhavan","year":"2017","journal-title":"PLoS One"},{"key":"ref99","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1007\/s00109-014-1189-3","article-title":"Systemic oxygenation weakens the hypoxia and hypoxia inducible factor 1\u03b1-dependent and extracellular adenosine-mediated tumor protection","volume":"92","author":"Hatfield","year":"2014","journal-title":"J Mol Med Berl Ger"},{"key":"ref100","doi-asserted-by":"crossref","first-page":"102647","DOI":"10.1016\/j.redox.2023.102647","article-title":"Hyperoxia induces glucose metabolism reprogramming and intracellular acidification by suppressing MYC\/MCT1 axis in lung cancer","volume":"61","author":"Liu","year":"2023","journal-title":"Redox Biol"},{"key":"ref101","doi-asserted-by":"crossref","first-page":"691762","DOI":"10.3389\/fonc.2021.691762","article-title":"Hyperbaric oxygen therapy represses the Warburg effect and epithelial-mesenchymal transition in hypoxic NSCLC cells via the HIF-1\u03b1\/PFKP axis","volume":"11","author":"Zhang","year":"2021","journal-title":"Front Oncol"},{"key":"ref102","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1080\/01902148.2019.1571124","article-title":"Hyperbaric oxygen rescues lung cancer cells from chemical hypoxia-induced low differentiation and apoptosis resistance","volume":"44","author":"Wang","year":"2018","journal-title":"Exp Lung Res"},{"key":"ref103","doi-asserted-by":"crossref","first-page":"E1180","DOI":"10.1152\/ajpendo.00499.2005","article-title":"Hyperoxia decreases muscle glycogenolysis, lactate production, and lactate efflux during steady-state exercise","volume":"290","author":"Stellingwerff","year":"2006","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"ref104","doi-asserted-by":"crossref","first-page":"101458","DOI":"10.1016\/j.nantod.2022.101458","article-title":"Hyperbaric oxygen regulates tumor mechanics and augments Abraxane and gemcitabine antitumor effects against pancreatic ductal adenocarcinoma by inhibiting cancer-associated fibroblasts","volume":"44","author":"Wang","year":"2022","journal-title":"Nano Today"},{"key":"ref105","first-page":"e2100233","article-title":"Hyperbaric oxygen boosts PD-1 antibody delivery and T cell infiltration for augmented immune responses against solid tumors","volume":"8","author":"Liu","year":"2021","journal-title":"Adv Sci Weinh Baden-Wurtt Ger"},{"key":"ref106","doi-asserted-by":"crossref","first-page":"1700859","DOI":"10.1002\/advs.201700859","article-title":"Hyperbaric oxygen potentiates doxil antitumor efficacy by promoting tumor penetration and sensitizing cancer cells","volume":"5","author":"Wu","year":"2018","journal-title":"Adv Sci"},{"key":"ref107","doi-asserted-by":"crossref","first-page":"2300162","DOI":"10.1002\/anbr.202300162","article-title":"Hyperbaric oxygen-facilitated cancer treatment: a minireview","volume":"4","author":"Li","year":"2024","journal-title":"Adv NanoBiomed Res"},{"key":"ref108","unstructured":"Gawdi R, Yrastorza J, Cooper JS. Hyperbaric oxygen therapy contraindications. StatPearls. Treasure Island (FL): StatPearls Publishing; 2025 [cited 2025 May 13]. Available from: http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK557661\/."},{"key":"ref109","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1016\/j.jtho.2022.12.021","article-title":"CD73 inhibitor oleclumab plus osimertinib in previously treated patients with advanced T790M-negative EGFR-mutated NSCLC: a brief report","volume":"18","author":"Kim","year":"2023","journal-title":"J Thorac Oncol"},{"key":"ref110","doi-asserted-by":"crossref","first-page":"9047","DOI":"10.1200\/JCO.2021.39.15_suppl.9047","article-title":"Safety and efficacy of the anti-CD73 monoclonal antibody (mAb) oleclumab \u00b1 durvalumab in patients (pts) with advanced colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), or EGFR-mutant non-small cell lung cancer (EGFRm NSCLC)","volume":"39","author":"Bendell","year":"2021","journal-title":"J Clin Oncol"},{"key":"ref111","doi-asserted-by":"crossref","first-page":"e1208875","DOI":"10.1080\/2162402X.2016.1208875","article-title":"Targeting CD73 in the tumor microenvironment with MEDI9447","volume":"5","author":"Hay","year":"2016","journal-title":"OncoImmunology"},{"key":"ref112","doi-asserted-by":"crossref","first-page":"7165","DOI":"10.1002\/jcp.26743","article-title":"Anti-angiogenic effects of CD73-specific siRNA-loaded nanoparticles in breast cancer-bearing mice","volume":"233","author":"Ghalamfarsa","year":"2018","journal-title":"J Cell Physiol"},{"key":"ref113","doi-asserted-by":"crossref","first-page":"e005267","DOI":"10.1136\/jitc-2022-005267","article-title":"Phase 1 first-in-human study of dalutrafusp alfa, an anti-CD73-TGF-\u03b2-trap bifunctional antibody, in patients with advanced solid tumors","volume":"11","author":"Tolcher","year":"2023","journal-title":"J Immunother Cancer"},{"key":"ref114","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1158\/1535-7163.MCT-23-0865","article-title":"Characterization of AB598, a CD39 enzymatic inhibitory antibody for the treatment of solid tumors","volume":"23","author":"Anderson","year":"2024","journal-title":"Mol Cancer Ther"},{"key":"ref115","doi-asserted-by":"crossref","first-page":"1838036","DOI":"10.1080\/19420862.2020.1838036","article-title":"Fully human anti-CD39 antibody potently inhibits ATPase activity in cancer cells via uncompetitive allosteric mechanism","volume":"12","author":"Spatola","year":"2020","journal-title":"mAbs"},{"key":"ref116","doi-asserted-by":"crossref","first-page":"e17553","DOI":"10.1200\/JCO.2024.42.16_suppl.e17553","article-title":"Enhanced anti-ovarian cancer efficacy with MSLN-chimeric antigen receptor T cells secreting anti-CD39 antibody","volume":"42","author":"Zhu","year":"2024","journal-title":"J Clin Oncol"},{"key":"ref117","doi-asserted-by":"crossref","first-page":"4003","DOI":"10.3390\/cancers14164003","article-title":"5-ALA is a potent lactate dehydrogenase inhibitor but not a substrate: implications for cell glycolysis and new avenues in 5-ALA-mediated anticancer action","volume":"14","author":"Grigalavicius","year":"2022","journal-title":"Cancers"},{"key":"ref118","doi-asserted-by":"crossref","first-page":"116736","DOI":"10.1016\/j.biopha.2024.116736","article-title":"12-O-deacetyl-phomoxanthone A inhibits ovarian tumor growth and metastasis by downregulating PDK4","volume":"175","author":"Yang","year":"2024","journal-title":"Biomed Pharmacother Biomedecine Pharmacother"},{"key":"ref119","doi-asserted-by":"crossref","first-page":"107115","DOI":"10.1016\/j.ultsonch.2024.107115","article-title":"Alleviating tumor hypoxia and immunosuppression via sononeoperfusion: a new ally for potentiating anti-PD-L1 blockade of solid tumor","volume":"112","author":"Yang","year":"2025","journal-title":"Ultrason Sonochem"},{"key":"ref120","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.1002\/mc.23045","article-title":"Antitumor activity of potent pyruvate dehydrogenase kinase 4 inhibitors from plants in pancreatic cancer","volume":"58","author":"Tambe","year":"2019","journal-title":"Mol Carcinog"},{"key":"ref121","doi-asserted-by":"crossref","first-page":"e1904639","DOI":"10.1002\/adma.201904639","article-title":"Intra\/Extracellular lactic acid exhaustion for synergistic metabolic therapy and immunotherapy of tumors","volume":"31","author":"Gao","year":"2019","journal-title":"Adv Mater Deerfield Beach Fla"},{"key":"ref122","doi-asserted-by":"crossref","first-page":"7771","DOI":"10.3390\/ijms24097771","article-title":"Metabolic effects of new glucose transporter (GLUT-1) and lactate dehydrogenase-A (LDH-A) inhibitors against chemoresistant malignant mesothelioma","volume":"24","author":"Franczak","year":"2023","journal-title":"Int J Mol Sci"},{"key":"ref123","doi-asserted-by":"crossref","first-page":"4480","DOI":"10.1111\/febs.16818","article-title":"Metformin exerts antileukemic effects by modulating lactate metabolism and overcomes imatinib resistance in chronic myelogenous leukemia","volume":"290","author":"Gayatri","year":"2023","journal-title":"FEBS J"},{"key":"ref124","doi-asserted-by":"crossref","first-page":"102240","DOI":"10.1016\/j.nano.2020.102240","article-title":"Silencing adenosine A2a receptor enhances dendritic cell-based cancer immunotherapy","volume":"29","author":"Masjedi","year":"2020","journal-title":"Nanomedicine Nanotechnol Biol Med"},{"key":"ref125","first-page":"6605","article-title":"Targeting the monocarboxylate transporter MCT2 and lactate dehydrogenase A LDHA in cancer cells with FX-11 and AR-C155858 inhibitors","volume":"27","author":"Alobaidi","year":"2023","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"ref126","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1007\/s12262-020-02601-4","article-title":"A randomised clinical trial to compare the efficacy of hyperbaric oxygen therapy with neoadjuvant chemotherapy with neoadjuvant chemotherapy alone for carcinoma breast: a pilot study","volume":"83","author":"Aphale","year":"2021","journal-title":"Indian J Surg"},{"key":"ref127","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1001\/jamaoncol.2023.6776","article-title":"Hyperbaric oxygen therapy and late local toxic effects in patients with irradiated breast cancer: a randomized clinical trial","volume":"10","author":"Mink Van Der Molen","year":"2024","journal-title":"JAMA Oncol"},{"key":"ref128","unstructured":"Hu Y, Sarkar A, Song K, Michael S, Hook M, Wang R, et al. Selective refueling of CAR T cells using ADA1 and CD26 boosts antitumor immunity. Cell Rep Med. [cited 2025 May 13]. Available from: https:\/\/www.cell.com\/cell-reports-medicine\/abstract\/S2666-3791(24)00199-X."},{"key":"ref129","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1089\/hum.2021.050","article-title":"Adenosine deaminase 1 overexpression enhances the antitumor efficacy of chimeric antigen receptor-engineered T cells","volume":"33","author":"Qu","year":"2022","journal-title":"Hum Gene Ther"},{"key":"ref130","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.canlet.2014.01.032","article-title":"Hypoxia and hypoxia inducible factors in tumor metabolism","volume":"356","author":"Zeng","year":"2015","journal-title":"Cancer Lett"},{"key":"ref131","doi-asserted-by":"crossref","first-page":"e190","DOI":"10.1038\/oncsis.2015.50","article-title":"Hypoxia and metabolic adaptation of cancer cells","volume":"5","author":"Eales","year":"2016","journal-title":"Oncogenesis"},{"key":"ref132","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1111\/imm.12380","article-title":"Hypoxia-inducible factors in regulation of immune responses in tumour microenvironment","volume":"143","author":"Kumar","year":"2014","journal-title":"Immunology"},{"key":"ref133","doi-asserted-by":"crossref","first-page":"3699","DOI":"10.1172\/JCI84431","article-title":"HIF1\u03b1 and metabolic reprogramming in inflammation","volume":"126","author":"Corcoran","year":"2016","journal-title":"J Clin Invest"}],"container-title":["Oncology Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.techscience.cn\/files\/or\/2025\/TSP_OR-33-8\/OncolRes-33-08-65953\/OncolRes-33-65953.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T01:55:12Z","timestamp":1763344512000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.techscience.com\/or\/v33n8\/63060"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025]]},"references-count":133,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025]]},"published-print":{"date-parts":[[2025]]}},"URL":"https:\/\/doi.org\/10.32604\/or.2025.065953","relation":{},"ISSN":["1555-3906"],"issn-type":[{"value":"1555-3906","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025]]}}}